The term “template-directed synthesis” includes the formation of a new substance by chemical modification of a substrate, or by the coupling of two or more molecules in the presence of a template which serves as a pattern for new structure formation. The most well-known example of this process is gene transcription. A particular example of template-directed synthesis is template polymerization, where formation of polymeric receptor (replica) proceeds in the presence of another polymer or small molecular weight organic substance-template. Prior to the initiation of polymerization, and during polymerization, the monomers spatially distribute themselves (self-assembling process) around the template molecules in accordance with the size, polarity and functionality of the template. The monomers are polymerized into either linear chains or rigid three-dimensional networks.
The specific example of template polymerization is molecular imprinting, based on polymerization of vinyl or acrylic monomers in the presence of template (see ref. 1, 2). The traditional approach involves the production of highly cross-linked imprinted polymers, which are insoluble in water and organic solvents. Because of their inherent insolubility, the possibility to use molecularly imprinted polymers (MIPs) in pharmacology and medicine is restricted.
Recently, several attempts have been made in order to develop protocols for the preparation of imprinted polymers with relatively low-molecular weights which could exist in soluble or at least colloidal forms. This format will allow polymers to be used as biologically active molecules (drugs, effectors, modulators, inhibitors) in pharmacology and medicine and as truly “plastic antibodies” in sensors and in affinity separation.
In one such example, MIP molecules were synthesized by a polycondensation of amino acids and nucleotides around a biological receptor, enzyme, nucleic acid, cell, virus, micro organism, tissue sample or drug (see U.S. Pat. No. 6,852,818). In another example, different methods were used to produce oligomeric and polymeric MIPs (see U.S. Pat. No. 6,127,154) Most of the examples in the prior art describe preparation of high-molecular weight cross-linked polymers which require hydrolysis for delivering soluble or colloidal particles stable in solution. In one such example (see U.S. Pat. No. 6,127,154) researchers used specially designed compounds containing photoactive perfluorophenylazido groups capable of coupling upon illumination. In this case oligomers could be synthesised as soluble particles. In all of these cases, synthesized compounds have fractions with poorly controlled size and properties. Other approaches for synthesis of MIPs with biological activity are described in WO 96/40822 and U.S. Pat. No. 5,630,978, where biologically-active molecules were prepared in the presence of template-imprinted polymer, which in turn were prepared in the presence of another template, normally a drug such as heparin. The resulting replica resembles the structure of the original drug molecule. It can hardly be expected that the activity of molecules synthesized in this way can be more pronounced than that of original template.
The living free-radical polymerization techniques, such as iniferter polymerization, nitroxide-mediated radical polymerization, atom-transfer radical polymerization (ATRP) and reversible addition-fragmentation chain-transfer (RAFT) polymerization, open new routes for the synthesis of polymers with controlled relatively low-molecular weights (see ref. 3-9). Controlled/living polymerization techniques are based on a delicate balance between dormant and active species that effectively reduces the concentration of free radicals in the system and minimizes the extent of termination. Living polymerization could be free of side reactions such as termination and chain transfer and thus can generate polymers with well defined molecular weight distribution and structure. The same approach can be applied to copolymers, thus making it possible to produce block copolymers by free radical polymerisation by proper sequencing of the monomer additions.
Living polymerization has been used previously in producing bulk grafted MIPs (see ref. 10, 11). The soluble polymers were also produced by living polymerization and used later in MIP production (see ref. 12). However, no one so far has developed soluble MIPs by living polymerization.
Background material can be found in the following references.    1. Wulff, G. Makromol. Chem. Macromol. Symp., 1993, 70/71, 285.    2. Viatakis, G.; et al. Nature, 1993, 361, 645.    3. Moad, G.; Rizzardo E.; Solomon, D. H. Macromolecules 1982, 15, 909;    4. Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921.    5. Kamigaito, M.; Ando, T.; Sawamoto, M. Chem. Rev. 2001, 101, 3689.    6. Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. Rev. 2001, 101, 3661.    7. Fischer, H. Chem. Rev. 2001, 101, 3581.    8. Otsu, T.; Matsumoto, A. Adv. Polym. Sci. 1998, 136, 75-137.    9. Moad, G.; et al. Polym. Int. 2000, 49, 993-1001.    10. Ruckert, B.; Hall, A. J.; Sellergren B. J. Mater. Sci. 2002, 12, 2275.    11. Hattori, K.; et al. J. Membr. Sci. 2004, 233, 169.    12. Li, Z.; Day, M.; Ding, J. F.; Faid, K. Macromolecules. 2005, 38, 2620.    13. Jagur-Grodzinski, J. Reactive & Functional Polymers. 2001, 1, 1.    14. Shim, S. E. et al. Macromolecules. 2003, 36, 7994-8000.    15. Yu, Q.; Zeng, F.; Zhu S. Macromolecules. 2005, 34, 1612.    16. U.S. Pat. No. 5,994,110    17. WO 96/41173